Each of the four heart valves in the human heart, the aortic, and mitral valves on the left side, or the pulmonary and tricuspid valves on the right side can become dysfunctional in many ways at any time. Such events including infections, structural failures such as tears or disruption of certain components as with the mitral valve chordae, or deformation because of genetic predisposition of valvular material, can disrupt the normal unidirectional flow of blood in the heart and the rest of the body often with fatal consequences. Cardiac valves perform a critical function in maintaining every tissue in the body with an adequate supply of nutrients, carried by the blood, as well as maintaining pulsatile flow through the vasculature to perfuse various organs in the body. Often when there are congenital malformations of some or all of these valves diseased at birth, an infant's life depend on quick and well-structured repair or replacement of the valves.
The development of external cardiopulmonary oxygenation with the heart lung machine made it possible to stop the heart to ease surgery to repair or replace the diseased or dysfunctional valves to save lives in spite of the trauma. The invasiveness of open chest and, open heart surgery and post-surgical complications inherent in such surgeries, also places the older population at high risk for mortality. The old and frail are often denied surgery after risk assessment and are treated instead with a range of relatively ineffective medications to make the effects of the valve disorder more bearable while patients continue an inevitable decline until death.
The use of catheter techniques to deliver and implant vascular stents in the coronary arteries to recanalize or dilate these arteries, to preserve blood flow to the heart muscle, allowed the removal of the blockage and the restoration of blood and oxygen flow to the heart muscle. Such techniques have become routine as millions of catheter-delivered stents have been placed worldwide in a relatively safe and effective manner. The techniques inspired pioneering developers in the cardiac value field to attempt to deliver heart valves in a similar manner. The technique depends on the ability to produce a frame or stent that houses a valvular mechanism, termed a valved stent, made of materials that can maintain their structure and that may be introduced through the vasculature and guided while mounted on a catheter. The valved stent is often placed within a capsule incorporated at the distal tip of the catheter to minimize damage to it and to the vessel walls during placement. When the tip is near the diseased valve, the valved stent is then allowed to emerge from the capsule on the catheter, expand by itself or with aid of balloons dilated with liquid pressure, to reach the nominal size of the device. Then the stent is deployed and deposited at the proper target site wherein the valved stent will remain and the valve will perform the intended function to replace the function of the diseased dysfunctional valve.
In addition to the vascular route, catheters containing the valved stent may be introduced into the heart in antegrade route, meaning following the flow of blood along a vessel or through the heart. Alternatively, a replacement valve may be introduced in retrograde manner, i.e. with the tip going against the flow of blood. If an aortic valved stent is introduced through the femoral artery, the catheter travels retrograde to the flow of blood, through the aorta until it reaches the diseased aortic valve where it will be deposited. An antegrade route can be found if the aortic valve is reached through the tip of the heart, by puncturing the tip, although this approach requires surgical entry through an incision between the ribs and guiding the catheter through the ventricle towards the left ventricular outflow tract that leads directly to the aortic valve. This is termed a transapical route.
This route could also be used in retrograde fashion to deposit a mitral valved stent at the mitral valve annulus between the left ventricle and left atrium, the tip containing the valved stent travels retrograde against the blood flow that is proceeding towards the aorta. However, a mitral valved stent delivered through the venous side would penetrate at the femoral vein, proceed through the vena cava to the right atrium, and pass through the wall that separates the upper chamber of the left side of the heart, the left atrium, the trans-septal route. In this approach, a puncture of the wall, also called a septum, must be made to allow the catheter tip to reach the atrium and to direct its tip to the mitral valve annular plane where the deposition of the valved stent occurs. This antegrade route is clearly a short-cut without major surgical technique, to the atrium and the dysfunctional mitral valve. The first aortic valves implanted by catheter guidance were in fact done in this manner, the catheter passed through the septum, through the mitral valve and through the chordal mass and continued to reach the aorta at the base of which one finds the diseased aortic valve and where the aortic valved stent was deposited. In the case of the mitral valve, another possible route is the transatrial route, another antegrade route that is a minimally invasive surgical technique through a relatively small incision through the chest that allows approach to the cranial or superior aspect, the roof of the left atrium, through which the valved stent bearing catheter can be introduced by following a direct path with the flow of blood to deposit the device into the dysfunctional mitral valve.
At present, the choice of technique depends on the condition of the patient and to minimize longitudinal or post intervention complications. While the catheter-guided techniques for the aortic and pulmonary valves have been used extensively, now counting over 300,000 patients, these techniques have not yet translated into well-established mitral valve replacement techniques. The obvious reason for this is the complexity of the mitral valve. The mitral apparatus consists of a continuum that begins at the walls of the heart from which papillary muscles emerge that connect to a group of tendon-like filaments termed the chordae tendineae. These structures have the appearance of parachute ropes that reach into the mitral valve leaflets' edges. The leaflets themselves are of different shapes and sizes. The anterior mitral leaflet having larger surface that connects to the atrial curtain descending from the aorta, and the posterior mitral leaflet that attaches to the outer or posterior portion of the wall of the heart. Both of these leaflets and chordal mass are contained within a not-so-continuous structure generally termed the “annulus.” Approach from the atrial side or the ventricular side of the valve to its annular plane poses difficulties of navigation, not only for the approach, but for the accurate deposition of valved stents coaxially (stent lined with the central axis of the mitral valve), and the capture of the necessary leaflet and annular components to remain in place, to seal the periphery between the two chambers, and to provide the necessary function.
Open surgical replacement has been performed for hundreds of thousands cases of mitral valve dysfunction until it was realized that the valvular tissue in some disorders was still well preserved in whole or in part. Top surgeons devised procedures to repair the malfunction in open heart procedures, although only recognized centers of excellence in cardiac surgery are able to perform the complex surgery. The number of patients affected with the condition of mitral regurgitation or valve incompetence graded in terms of its severity at higher than mild (moderate) and many graded severe is very large reaching many millions worldwide. Oern S, Liddicoat J.: Emerging Opportunities for Cardiac Surgeons within Structural Heart Disease. J Thorac and Cardiovasc Surgery: 132: 1258-1261 (2006), authors describe the incidence of disorders of the cardiac valves in the USA population, and show that on the order of 2.3 million patients yearly have dysfunctional mitral valves in various stages, with approximately 220,000 in the severe category. Of these severe patients, only about 23% (48,000) receive the proper treatment for correction of the condition. Regrettably, a large proportion goes untreated and since the report was written over one million patients have died. Present day mitral valve repair centers can only handle a few of the afflicted.
The translation of surgical repair techniques to catheter-guided less invasive techniques began in the late 1990s in the hope of enabling mitral valve surgical repair techniques. This hope was met with many disappointments when assessing the reliability of the safety and more particularly the effectiveness of such procedures. The results in many cases are only partially satisfactory with a sizable percentage of incomplete repairs of mitral regurgitation. Although a variety of approaches have been attempted, trapping the mitral valve leaflets' central edges and apposing them centrally thus creating a double orifice (reproducing the surgical Alfieri edge-to-edge repair technique with catheters) to reduce mitral regurgitation is the most advanced. Others provide reduction of annular dilatation through the introduction of metallic wires through the coronary sinus vein to circumscribe the mitral valve annulus and reduce its size by constriction, but this also met with disappointing results. A few others purported to correct the condition by repair with minimally invasive procedures but the results are poor at best.
In various embodiments, replacement heart valves can comprise certain components that are common to most devices for replacement of heart valves. There is often a component that will act as support, the frame, usually referred to as the stent. Within this frame or stent, a valvular mechanism is enclosed, often having more flexibility in the case of the so called biological heart valves, as these valvular mechanisms are to undertake the restoration of the valvular function. These valvular mechanisms are comprised of sections of thin material (usually a biological membrane) that are movable under the action of the flow of blood. These sections that can be singular or be in a plurality of two or more sections often termed the “leaflets” or “valves.” Depending on the direction of the flow of blood, these surfaces will move in the same direction, so as to open the orifice that is provided by the stent as large as possible without damage to the leaflet when blood flows from one chamber of the heart to the next or towards the outside the heart. Subsequently, as the pumping stroke of the heart is finished, blood flow reversal occurs instantaneously and pushes the leaflets in the opposite direction closing the valve and impeding retrograde blood flow or reflux, also called regurgitation. Regurgitation can greatly diminish the efficiency of the heart and is considered a serious, often life-threatening condition.
The valves used for decades as implants for the major part consisted of the same components, namely a stent generally fabricated from polymers reinforced with wire, and a leaflet mechanism. The valved stents of the “new era” of valve therapy, are in general cylindrical tubular frames of metal, cut in such manner and shape to be compressed to a very small diameter, close to the original diameter of the tube while including the tissue valvular mechanism, such that the whole valve can be threaded through the vasculature with the aid of catheters, in the smaller possible profile. These metal stents are generally made of rust-free very pure stainless steels (alloys of iron and other metals) that require a liquid filled balloon under pressure to be expanded to their final or nominal diameter. However, in their final expanded diameter, such stents are still heir to the pressures the tissue may apply and can be deformed inwardly resulting in loss of the function attempted to restor. Other metal alloys used are the so-called shape memory metals that can be compressed to the small diameters desired at specified low temperature ranges and on their own, because of their molecular composition, will expand under temperature (i.e. body temperature) to their original pre-compression nominal diameter. The stents, in effect the valves, in the “new era” of heart valve therapy are conformed to meet specified and stringent requirements to perform the needed function, specifically, the ability to remain in the target site at the native annulus without dislocating or migrating, such that the replacement valve remains anchored in place for the rest of the patient's life. Valve function is needed. In addition, the valved stent must seal the periphery to avoid leakages (some leakages are in effect regurgitation) that can be very damaging to the blood and the health of the patient, and otherwise may require revision or surgery for correction.
The use of stents in aortic valve replacement therapy is mostly for aortic stenosis, a disease that often occurs because of the pathological mineralization of the tissue that constitutes the aortic heart valve. Leaflets of the aortic valve become thickened and calcium deposits by diffusion from the blood plasma within the leaflet tissue and at times on the surface of the tissue, hardening the leaflets and their mobility to the point that they practically close by narrowing (stenosis) the orifice leading from the left ventricle to the aorta so that blood cannot follow a normal flow. The ventricle pumping overexerts its muscle which becomes thickened trying to pump blood through a smaller orifice of the aortic valve and slowly its function decays. The body is deprived of blood and organ conditions and quality of life decreases rapidly. Catheter-guided implanted valved stents that are used to correct the disease rely on purely the force exerted by the stent on the calcified rocky leaflets. These stents are cylindrical in the neighborhood of the valve and the walls of the cylinder exert the pressure that keeps the valved stent in the area of the native aortic valve. This pressure will be exerted by dilation of the stainless steel valved stent with a balloon, or by the temperature shape memory force the expanded stent can exert. It is an entirely different set of conditions that are present in the case of mitral valve regurgitation.
Mitral regurgitation (MR) can be caused by many conditions of which some are more amenable to the use of valved stents. One form that results from changes in the shape and size of the heart, by dilatation of both heart and mitral valve annulus (dilated cardiomyopathy, DCM) results in alteration of the valvular function and as such is termed “functional mitral regurgitation.” It is a vicious cycle, when myocardial (heart muscle) damage results in left ventricle dilation which in turns leads to apical dislodgement of the papillary muscle, leading to annular dilatation. These two effects combine to produce mitral regurgitation causing left ventricle overload and that in turn results in left ventricle dilatation and the cycle begins again. When the annulus, the mitral valve, and the atrial curtain lose the ability to maintain the size of the mitral valve orifice, dilatation can expand this orifice to almost double its size in extreme cases. In such cases, the valve leaflets are far apart at a time in the heart cycle (systole) when they should be in apposition and closing the valve orifice to impede reflux into the chamber (atrium). The annulus is soft and somewhat pliable and exerting pressure radially as is done with the aortic stents lead to more expansion thereby aggravating the condition.
Currently, no prosthetic mitral valve devices have been fully developed and commercialized for placement in a dysfunctional mitral valve or replacement of the native mitral valve function by percutaneous means or catheter-guided means. A very strong need exists for improved designs of valved stents, and devices of delivery that will result in improved embodiments to replace the function of mitral heart valves, and tricuspid valves. These devices must enable the precise delivery, deployment, and deposition of valved stents into the atrioventricular annuli and their engagement with minimal complications and restoration of function as near as possible to that of normal healthy human valves. These devices must also prevent the development of peripheric valvular leaks (PVL), the development of leaks between the implanted valved stent and the native valular tissue, to which the valve stent must conform very closely. These conditions also require that the valve be operatively paired with a specially designed valve stent and a specially designed delivery system.